Insulin is thought to be an important hormone in the regulation and control of growth of the fetus of late gestation. Macrosomic infants borne to diabetic women and growth retarded fetuses with absence of the pancreas appear to offer naturally occuring instances of the effects of either insulin excess or deficiency upon fetal growth. The goals of the proposed work are: a) to define the metabolic and growth related effects of chronic insulin secretory deficiency using both sheep and rabbit models of intrauterine growth; b) to explore further the previously made observations that fetal hyperglycemia induces a dramatic increase in fetal metabolic rate and placental lactate production. In fetal lambs, glucose induced changes in muscular work and cerebral metabolism and function will be observed. In rabbits, the effects of chronic hyperglycemia upon fetal growth, with particular emphasis upon fetal fat synthesis, will be studied; c) the effects of superimposed asphyxia upon chronic fetal hyperglycemia will be investigated to test the hypothesis that glucose induced increase in fetal and fetal cerebral metabolic rate and in placental lactate delivery to the fetus may place such fetuses at a great risk of hypoxia induced white matter injury, the forerunners of cerebral palsy. In portion a) fetal injection of streptozotocin into chronically catheterized fetal lambs and fetal rabbits will be used to explore the relationship between insulin secretory rate and umbilical substrate uptake and consequent fetal growth. In portion b) chronic glucose infusions into either mothers (rabbits) or fetuses (lambs) will be given to study fetal metabolic rate changes and growth. In part c) using a fetal twin lamb model, the effects of superimposed hypoxia in hyperglycemic and control lambs can be assessed relative to histologic evidence of brain damage and correlated with both fetal electroencephalography and cerebral lactate concentrations.